JCO:吉西他滨+厄洛替尼辅助治疗胰腺导管腺癌,患者能否获益?

2017-08-26 肿瘤资讯编辑部 肿瘤资讯

胰腺导管腺癌是一类预后非常差的恶性肿瘤,缺乏有效的治疗靶点。在晚期胰腺癌中发现,吉西他滨联合厄洛替尼,相比吉西他滨单药显着延长OS。基于此,进行了CONKO-005研究,旨在R0切除术后的胰腺导管腺癌中,探索吉西他滨联合厄洛替尼对比吉西他滨单药,能否给患者带来生存获益。

胰腺导管腺癌是一类预后非常差的恶性肿瘤,缺乏有效的治疗靶点。在晚期胰腺癌中发现,吉西他滨联合厄洛替尼,相比吉西他滨单药显着延长OS。基于此,进行了CONKO-005研究,旨在R0切除术后的胰腺导管腺癌中,探索吉西他滨联合厄洛替尼对比吉西他滨单药,能否给患者带来生存获益。

背景

胰腺导管腺癌(PDAC)是少数几个病死率仍持续上升的恶性肿瘤,预计到2030年,PDAC有可能成为第二大常见的癌症相关死因。根治性手术切除是唯一可能治愈的治疗手段,但因为胰腺癌侵袭性强,且早期没有特异性的临床症状,因此仅有20%的患者在诊断时可切除。尽管外科手术技术不断发展,随着围术期处理的进步,90%以上的术后患者还是会复发。多中心随机对照临床试验(CONKO-001)显示,术后辅助吉西他滨化疗对比单纯观察,可以延长一倍的长期生存(>5年),治愈率增加达20%以上。氟尿嘧啶辅助治疗的临床研究ESPAC-3也显示了相似的长期生存。

厄洛替尼是口服EGFR-TKI,联合吉西他滨是第一个用于不可切除PDAC的联合方案,相比吉西他滨单药显着延长OS。在晚期患者中,姑息治疗有效的方案,在辅助治疗阶段有效的可能性非常大,基于此,开展了CONKO-005研究。该研究假设在辅助吉西他滨的基础上联合厄洛替尼用于R0切除术后的患者,可以显着改善患者的预后;此外,研究还探索性的分析了皮疹的发生能否预测治疗疗效。

方法

CONKO-005研究是一个开放的,多中心,随机对照III期临床研究,入组了R0切除术后的PDAC患者。所有的患者后续均以1:1随机分配接受吉西他滨+厄洛替尼或吉西他滨单药治疗。分层因素包括:手术方式(经典Whipple术 vs. 保留幽门胰十二指肠切除术 vs. 全胰腺切除术),淋巴结受累(N0 vs. N+)和研究中心。主要研究终点为无病生存期(DFS),定义为自随机至局部或远处复发或死亡的时间。

结果

经各中心筛查,共450例R0切除术后的PDAC符合入组条件,在经中心统一筛查后,共入组436例患者,如图1所示。患者随机分配至吉西他滨+厄洛替尼组(GemErlo [n = 219])或标准治疗吉西他滨单药组(Gem [n = 217])。两组的基线特征均衡,中位治疗周期都为154天(22周)。GemErlo和Gem组分别有145例(66%)和160例完成了方案既定的6周期化疗(n=305;P=0.045)。


图1. 入组患者流程图

药物毒性:

最常见的3-4度不良事件(AE)为中性粒细胞减少或白细胞减少、转氨酶升高、腹泻和乏力。

疗效:

中位随访54个月,试验组和对照组分别有80.8%(177/219)和84.8%(184/217)的患者复发。361例复发患者中,217例可以评估复发类型:GemErlo和Gem组的孤立局部复发的比例分别为24%和18%;远处复发(无论是否合并有局部复发)的比例分别为76%和82%;主要的远处复发部位为肝脏,分别为31%和33%。

生存分析:

GemErlo和Gem组预估的中位DFS分别位11.4个月(95%CI:9.8-12.9)和11.4个月(95%CI:9.6-13.2),两组无统计学差异(HR=0.94;95%CI:0.76-1.15;P=0.26),见下图2A。预估的1年、2年和5年DFS率分别位48%,25%和12%(GemErlo和Gem组分别为47%,26%和13%和48%,25%和11%)。在ITT人群中,中位OS为26.2个月(95%CI:23.3-29.1),两组的OS分别为24.5(95%CI:21.1-27.8)和26.5(95%CI:22.4-30.6)。预估的1年、2年和5年OS分别为78%,53%和23%,GemErlo组为77%,53%和25%;Gem组为79%,54%和20%,见下图2B。



图2. 两组DFS(A)和OS(B)对比。

对GemErlo组的219例患者进行亚组分析,治疗相关的皮疹发生级别与患者的DFS无相关性:0-1度皮疹和2-4度皮疹患者的中位DFS分别为12.1个月(95%CI:8.6-15.6)和11.0个月(95%CI:8.7-13.4),P=0.71;中位OS分别为24.0个月(95%CI:19.9-28.2)和25.9个月(95%CI:20.6-31.3);P=0.99。

CA19-9和患者总生存的关系:

336例患者的CA 19-9水平≤100 kU/L (GemErlo组167例,Gem组169例),中位DFS分别为12.2个月和13.1个月(P=0.626);中位OS分别为27.6个月和30.1个月(P=0.849)。54例患者术后CA 19-9有升高的,有显着更差的中位DFS和OS(P<0.001)。


图3. 根据术后不同CA 19-9水平进行DFS(A)和OS(B)对比。

患者在术后6周内对比术后6周(≤42天 vs. >42天)以上进行辅助化疗的,有更差的DFS,分别为10.9个月(95%CI:9.4-12.4)和12.2个月(95%CI:9.6-14.7),P=0.026。但这一DFS的获益没有转化为OS的获益:分别为27.3m(95%CI:24.3-30.2)和24.3m(95%CI:20.2-28.5),P=0.94.

结论

CONKO-005是一项在胰腺腺癌中进行的仅纳入R0切除术后的III期研究,也是第一个多中心、前瞻性的随机对照临床研究,在原发性可切除的PDAC患者中比较化疗联合靶向治疗对比单纯化疗。研究没有达到主要终点,在R0切除术后的PDAC患者中,在辅助化疗的基础上联合厄洛替尼并没有带来DFS的获益,在OS上,吉西他滨联合厄洛替尼组5年OS有获益趋势(分别为25% vs. 20%),但没有统计学差异。

讨论与点评

从CONKO-005研究结果来看,PDAC患者中应用EGFR-TKI的作用仍不明确。在PDAC患者中,KRAS的突变率非常高(超过95%),这是否会导致EGFR TKI的耐药,目前尚不明确。哪一类型的PDAC患者可以从EGFR-TKI的治疗中获得最大获益,目前有待考量。近期,一项回顾性的研究根据PDAC患者的基因和表达模式,将其分为3类:经典型、间叶细胞样和内分泌样,在鼠模型中显示内分泌样亚型与厄洛替尼的耐药显着相关。后续将利用CONKO-005研究中收集的患者标本进行探索性分析,期待能在PDAC患者中发现真正能从EGFR-TKI治疗中获得最大获益的患者。

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (6)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1891427, encodeId=c156189142e1a, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Thu Jul 05 00:52:00 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332072, encodeId=77b313320e24b, content=<a href='/topic/show?id=f19136915a9' target=_blank style='color:#2F92EE;'>#厄洛替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36915, encryptionId=f19136915a9, topicName=厄洛替尼)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/6F20312C71B4B22F603078C6DCFA72CE/100, createdBy=d3572500071, createdName=ms306040998833292, createdTime=Mon Aug 28 11:52:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237573, encodeId=9b8923e5737d, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sun Aug 27 07:01:39 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237562, encodeId=4fd223e56210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:53:30 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237558, encodeId=34e823e55825, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:51:59 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237549, encodeId=a0ac23e549bb, content=文章真好.值得分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sun Aug 27 06:40:36 CST 2017, time=2017-08-27, status=1, ipAttribution=)]
    2018-07-05 lidong40
  2. [GetPortalCommentsPageByObjectIdResponse(id=1891427, encodeId=c156189142e1a, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Thu Jul 05 00:52:00 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332072, encodeId=77b313320e24b, content=<a href='/topic/show?id=f19136915a9' target=_blank style='color:#2F92EE;'>#厄洛替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36915, encryptionId=f19136915a9, topicName=厄洛替尼)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/6F20312C71B4B22F603078C6DCFA72CE/100, createdBy=d3572500071, createdName=ms306040998833292, createdTime=Mon Aug 28 11:52:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237573, encodeId=9b8923e5737d, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sun Aug 27 07:01:39 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237562, encodeId=4fd223e56210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:53:30 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237558, encodeId=34e823e55825, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:51:59 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237549, encodeId=a0ac23e549bb, content=文章真好.值得分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sun Aug 27 06:40:36 CST 2017, time=2017-08-27, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=1891427, encodeId=c156189142e1a, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Thu Jul 05 00:52:00 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332072, encodeId=77b313320e24b, content=<a href='/topic/show?id=f19136915a9' target=_blank style='color:#2F92EE;'>#厄洛替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36915, encryptionId=f19136915a9, topicName=厄洛替尼)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/6F20312C71B4B22F603078C6DCFA72CE/100, createdBy=d3572500071, createdName=ms306040998833292, createdTime=Mon Aug 28 11:52:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237573, encodeId=9b8923e5737d, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sun Aug 27 07:01:39 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237562, encodeId=4fd223e56210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:53:30 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237558, encodeId=34e823e55825, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:51:59 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237549, encodeId=a0ac23e549bb, content=文章真好.值得分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sun Aug 27 06:40:36 CST 2017, time=2017-08-27, status=1, ipAttribution=)]
    2017-08-27 三生有幸9135

    学习一下谢谢分享

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1891427, encodeId=c156189142e1a, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Thu Jul 05 00:52:00 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332072, encodeId=77b313320e24b, content=<a href='/topic/show?id=f19136915a9' target=_blank style='color:#2F92EE;'>#厄洛替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36915, encryptionId=f19136915a9, topicName=厄洛替尼)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/6F20312C71B4B22F603078C6DCFA72CE/100, createdBy=d3572500071, createdName=ms306040998833292, createdTime=Mon Aug 28 11:52:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237573, encodeId=9b8923e5737d, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sun Aug 27 07:01:39 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237562, encodeId=4fd223e56210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:53:30 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237558, encodeId=34e823e55825, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:51:59 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237549, encodeId=a0ac23e549bb, content=文章真好.值得分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sun Aug 27 06:40:36 CST 2017, time=2017-08-27, status=1, ipAttribution=)]
    2017-08-27 yfjms

    学习了

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1891427, encodeId=c156189142e1a, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Thu Jul 05 00:52:00 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332072, encodeId=77b313320e24b, content=<a href='/topic/show?id=f19136915a9' target=_blank style='color:#2F92EE;'>#厄洛替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36915, encryptionId=f19136915a9, topicName=厄洛替尼)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/6F20312C71B4B22F603078C6DCFA72CE/100, createdBy=d3572500071, createdName=ms306040998833292, createdTime=Mon Aug 28 11:52:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237573, encodeId=9b8923e5737d, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sun Aug 27 07:01:39 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237562, encodeId=4fd223e56210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:53:30 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237558, encodeId=34e823e55825, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:51:59 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237549, encodeId=a0ac23e549bb, content=文章真好.值得分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sun Aug 27 06:40:36 CST 2017, time=2017-08-27, status=1, ipAttribution=)]
    2017-08-27 yfjms

    学习了

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1891427, encodeId=c156189142e1a, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Thu Jul 05 00:52:00 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332072, encodeId=77b313320e24b, content=<a href='/topic/show?id=f19136915a9' target=_blank style='color:#2F92EE;'>#厄洛替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36915, encryptionId=f19136915a9, topicName=厄洛替尼)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/6F20312C71B4B22F603078C6DCFA72CE/100, createdBy=d3572500071, createdName=ms306040998833292, createdTime=Mon Aug 28 11:52:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237573, encodeId=9b8923e5737d, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sun Aug 27 07:01:39 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237562, encodeId=4fd223e56210, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:53:30 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237558, encodeId=34e823e55825, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Sun Aug 27 06:51:59 CST 2017, time=2017-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=237549, encodeId=a0ac23e549bb, content=文章真好.值得分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Sun Aug 27 06:40:36 CST 2017, time=2017-08-27, status=1, ipAttribution=)]
    2017-08-27 1e10c84am36(暂无匿称)

    文章真好.值得分享

    0

相关资讯

Sci Rep:miR-107的缺乏促进了胰腺癌的发展

血浆中肿瘤抑制因子miR-107的减少与肿瘤进展有关,是治疗胰腺癌新型靶点。本研究探讨胰腺癌(PCa)患者肿瘤抑制微小RNA(miRNA)血浆水平的降低,以阐明其作为新生物标志物和治疗靶点的潜力。研究使用基于microRNA阵列的方法通过比较PCa患者和健康志愿者的血浆水平来选择候选者。选择六个下调的miRNA(miR-107,miR-126,miR-451,miR-145,miR-491-5p和

Sci Rep:不同类型胰腺癌细胞中KRAS突变的异质性

胰腺导管腺癌(PDAC)是一种破坏性疾病,血液中的循环肿瘤细胞(CTC)被认为是全身肿瘤扩散的手段。PDAC是美国和欧洲癌症相关死亡的第四大原因,发生率几乎等于死亡率,5年生存率<6%。这主要是由于其在转移期经常晚期诊断,具侵袭性,并仅对部分已知化学疗法应答。

Sci Rep:胰腺癌细胞分泌的外泌体诱导C2C12肌管细胞胰岛素抵抗的机制

前瞻性流行病学研究均表明,胰腺癌相关的新发糖尿病(PC-DM)是胰腺癌(PC)早期诊断的一个潜在的表现。尽管已有许多研究,但是这种现象背后的机制仍然模糊不清。在这项研究中,研究人员探究了来源于小鼠胰腺癌和小鼠骨骼肌细胞的导管上皮细胞的两种外泌体的影响。结果表明,PC来源的外泌体能够轻易进入C2C12肌管,引发脂质和葡萄糖摄取抑制。此外,PC来源的外泌体还可抑制胰岛素和PI3K/Akt信号通路,由此

MOL CELL:诱发胰腺癌生长和扩散的“根源”已确定!

来自耶鲁大学的一项研究发现,胰腺癌细胞利用葡萄糖生存,并且扩散到其他器官。众所周知,胰腺癌是一种非常致命的疾病,胰腺癌患者不仅痛苦不堪,而且可供胰腺癌患者选择的治疗方法也是少之又少。然而,近期,由耶鲁大学领导的研究团队已经确定了一个基因,这种基因对胰腺癌细胞的生长至关重要,这一研究为新疗法确定了新目标。

JCO:散发胰腺癌患者的有害胚系突变

大家都知道有害的胚系突变导致胰腺癌易感性增加,这在多人患胰腺癌的家庭中也得到了证实。但在散发胰腺癌患者中这些突变频率如何呢?

Sci Rep:通过损伤细胞外囊泡REG3β可改变肿瘤细胞的功能

细胞外囊泡(EVs),包括外泌体和微泡,均是含有蛋白质和核酸可作为细胞间信使的纳米级囊泡。EVs不仅在各种生理过程中起着重要作用,在炎症或癌症等病理情况下也起着重要作用。该研究表明,在胰腺导管腺癌(PDAC)的情况下,肿瘤周围正常胰腺组织可释放的REG3β——存在EVs表面连接糖蛋白的一种凝集素,从而干扰靶细胞的摄入和内化。在体外,由于REG3β的存在可扰乱EVs介导的通路,防止EV介导巨噬细胞的